The present invention relates to the synthesis of organic compounds, and, more particularly, to the synthesis of certain ketoxime carbamates.
U.S. Pat. No. 3,875,232 and a number of subsequent related United States patents have issued to Thomas A. Magee disclosing and claiming certain novel ketoxime carbamate compositions. These compositions are described by the formula: ##STR1## where: R.sub.1 =hydrogen, R.sub.2 -R.sub.3 or X;
R.sub.2 -R.sub.3 =lower alkyl, lower alkenyl, lower alkynyl, substituted lower alkyl, alkenyl, or alkynyl with the proviso that R.sub.2 and R.sub.3 may be connected to form a cycloaliphatic ring; PA1 R.sub.6 -R.sub.7 =hydrogen, lower alkyl, lower alkenyl, or lower alkynyl; PA1 Y=H or X; PA1 X=is selected from the group consisting of SR.sub.8, S(O)R.sub.8, SO.sub.2 R.sub.8, OR.sub.8, OSO.sub.2 R.sub.8, NR.sub.8 R.sub.9, NO.sub.2, CN, SCN, N.sub.3, or halogen with the proviso that when X and Y are OR.sub.8, SR.sub.8, S(O)R.sub.8, SO.sub.2 R.sub.8, or NR.sub.8 R.sub.9, X and Y may be connected to form a heterocyclic ring; PA1 R.sub.8 =hydrogen, lower alkyl, lower alkenyl, lower alkynyl, aryl, substituted aryl, carbamyl, substituted carbamyl, acyl, or substituted acyl with the proviso that the lower alkyl or alkenyl groups may be further substituted with X; and PA1 R.sub.9 =hydrogen or lower alkyl with the proviso that R.sub.8, R.sub.9 and N in the NR.sub.8 R.sub.9 group may form a heterocyclic ring. PA1 R.sub.2 -R.sub.3 =lower alkyl, lower alkenyl, lower alkynyl, substituted lower alkyl, alkenyl, or alkynyl with the proviso that R.sub.2 and R.sub.3 may be connected to form a cycloaliphatic ring; PA1 R.sub.6 -R.sub.7 =hydrogen, lower alkyl, lower alkenyl, or lower alkynyl; PA1 X-Y=X and Y may be the same or different and each is selected from the group consisting of SR.sub.8, S(O)R.sub.8, SO.sub.2 R.sub.8, OR.sub.8, OSO.sub.2 R.sub.8, NR.sub.8 R.sub.9, NO.sub.2, CN, SCN, N.sub.3, or halogen with the proviso that when X and Y are OR.sub.8, SR.sub.8, S(O)R.sub.8, SO.sub.2 R.sub.8, or NR.sub.8 R.sub.9, X and Y may be connected to form a heterocyclic ring; PA1 R.sub.8 =hydrogen, lower alkyl, lower alkenyl, lower alkynyl, aryl, substituted aryl, carbamyl, substituted carbamyl, acyl, or substituted acyl with the proviso that the lower alkyl or alkenyl groups may be further substituted with X; and PA1 R.sub.9 =hydrogen or lower alkyl with the proviso that R.sub.8, R.sub.9 and N in the NR.sub.8 R.sub.9 group may form a heterocyclic ring.
The term lower alkyl radical means a radical having from one to about seven carbon atoms.
According to Magee, the compounds can be prepared by one of three basic methods. The first method (referred to by Magee as Method A) involves reaction of an isocyanate with an oxime as shown, for example, in the equation: ##STR2## wherein R.sub.1 through R.sub.6 and X are defined above. The oxime and isocyanate are reacted in an inert organic solvent from about 0.degree. C. to about 150.degree. C., preferably from about 20.degree. C. to about 80.degree. C., and at a pressure from about 1 to 10 atmospheres, preferably from about 1 to about 3 atmospheres. Reaction pressure is determined by reaction temperature, concentration and vapor pressure of the isocyanate. Preferably, reaction is carried out in the presence of from about 0.1 to about 1.0 percent, by weight, based on the weight of reactants, of a tertiary amine catalyst such as triethyl amine, N,N-dimethylaniline, or the like. The molar ratio of isocyanate to oxime can vary from about 0.1:1 to about 10:1. An equimolar amount or slight excess of isocyanate is preferred to ensure complete reaction of the oxime. Reaction times can vary from a few minutes to several days. Usually, reaction times of from about one-half to about six hours are sufficient.
A second method (referred to by Magee as Method B) involves reaction of an oxime with phosgene to obtain an oxime chloroformate which is then reacted with an amine. This method is illustrated in Equations (1) and (2) below: ##STR3##
In the reaction shown in Equation (1), a solution of the oxime dissolved in an inert solvent as diethyl ether, is added slowly to a solution of phosgene dissolved in an inert solvent in the presence of an HCl acceptor such as a tertiary amine, e.g., N,N-dimethylaniline. Reaction is carried out from about -30.degree. C. to about 100.degree. C., preferably at from about 0.degree. C. to about 50.degree. C. The resulting reaction mixture, a solution of the chloroformate in an inert organic solvent, can be filtered or washed with water to remove amine hydrochloride before it is used in the reaction shown in Equation (2).
In the reaction shown in Equation (2), an amine is added to the chloroformate solution in the presence of an amine solvent such as water, at temperatures between about -40.degree. C. and about 80.degree. C., preferably at about 0.degree. C. to about 40.degree. C. A larger than molar excess of amine can be used so that the amine acts both as reactant and as HCl acceptor and complete conversion of chloroformate is obtained. Alternatively, a separate HCl acceptor, such as tertiary amine, can be used.
The third method (referred to by Magee as Method C) for the preparation of such compositions comprises reacting:
(a) a compound of the formula ##STR4## wherein Z is a reactive halogen, and
(b) HX,
in the presence of an HZ acceptor. This includes reaction of the haloketones with mercaptans or alcohols in the presence of an acid acceptor, e.g., sodium alkoxide. Sulfinyl and sulfonyl linked compounds can be prepared by oxidizing the appropriate sulfide linked compound with sodium metaperiodate or acidic hydrogen peroxide, respectively.
In most of the compounds prepared by Magee using the three above-described procedures, Y was hydrogen. Attempts to employ these procedures to synthesize compounds in which Y was a second X group using Method C produced only very small yields because of the number and variety of side reactions, and the oxime starting materials were not available for Methods A or B.
Another potential method of producing compounds where R.sub.5 is a second X moiety, would seem to be the oximation of 2-keto-1,1-dithioacetals as illustrated by the equation: ##STR5## However, this method also has a limited success apparently because of the steric hinderance of the dithioacetal group as confirmed by P. E. Pearson and O. D. Keaton in a 1963 article in the Journal of Organic Chemistry, Volume 28, page 1557.